Prolactin is a hormone secreted from cells of the anterior pituitary gland which may serve many roles in addition to that implied by its name. That is, other than promoting lactation in all mammals, prolactin has been shown to play a role in maintenance of progesterone secretion (and hence pregnancy) by the ovaries, as well as the immune response and osmoregulation in many mammals. Other than the classic nursing-induced release of prolactin secretion described in all mammals, a host of other stimuli such as stress and ovarian steroids also induce prolactin secretion. We have shown that the mating stimulus leads to 10 days of daily nocturnal and diurnal surges of prolactin secretion from the pituitary gland. This hormone is responsible for maintenance of the corpus luteum. During the 14 years we have had this grant we have described the neural circuitry as well as the role of the ovaries and uterus responsible for initiating and maintaining the surges of prolactin. During the previous granting period we have discovered why the rat has 2 surges of prolactin in response to the mating stimulus. We have found that there is an endogenous stimulatory rhythm originating in the hypothalamus and that the prolactin-releasing expression of this rhythm is masked by dopamine acting at the pituitary. The rhythm is unmasked by any dopamine-lowering stimulus such as mating. Using pharmacologic approaches and direct measurement we have identified OT as the neurohormone controlling the nocturnal and diurnal component of the rhythm and VIP as the neuromodulator controlling the nocturnal component while 5-HT controls the diurnal component. The specific aims of the present application are: (1) to characterize the anatomical and physiological relationship between the neuromodulators and neurohormones controlling the endogenous stimulatory rhythm and (2) to characterize the cellular mechanisms through which the lactotroph transduces the twice daily signal into prolactin secretion. These studies are important because they will identify the controls of prolactin secretion from the whole animal to the cellular level which are operative in not only mating but also other physiological states such as lactation. We provide evidence that the control of this endogenous stimulatory rhythm for prolactin secretion may be operative and generalizable to control of prolactin secretion in a host of other physiological states.